Uncontrolled proliferation is a hallmark of malignant lesions, including B cell lymphomas. Murine gammaherpesvirus MHV68, similar to human gammaherpesviruses, infects and remains latent in B cells and causes lymphoproliferative disorders and B cell lymphomas in infected animals. MHV68 induces proliferation of murine splenocytes and activation of B cells. The mechanisms of MHV68-induced cellular proliferation are not clear. The connection between MHV68-induced proliferation and lymphomagenesis has not been examined, but is likely to exist. Proposed studies focus on the understanding of viral and host factors involved in MHV68-driven B cell proliferation. In vitro experiments proposed in Aim 1 will test the hypothesis that MHV68-driven splenocyte proliferation is due to proliferation of B cells and is mediated by a secreted mitogen. In specific aim 2 MHV68 mutants will be used to determine a MHV68 gene product(s) that is responsible for B cell proliferation in vitro. A model of MHV68 lymphomagenesis will be used in Specific Aim 3 to test the hypothesis that MHV68 protein(s) required for B cell proliferation in vitro also play a role in MHV68-induced lymphomagenesis in vivo. [unreadable] [unreadable]